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Copper Deficiency Induces Oxidative Stress in Liver of Mice by Blocking the Nrf2 Pathway

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Abstract

Copper (Cu) is an essential metal required for many physiological processes and biological reactions. Liver is the main organ of metabolism of Cu and is also the site where synthesis of some metalloproteins. The purpose of this study is to explore the effects of Cu deficiency on the liver and to evaluate the changes in liver oxidative stress levels to reveal its possible impact mechanisms. Mice were feed to a nutritional Cu-deficiency diet from weaning and injected with copper sulfate (CuSO4) intraperitoneally to correct Cu deficiency. Cu deficiency resulted in reduced liver index, liver histological alteration, and oxidative stress; decreased the contents of Cu and ALB; elevated ALT and AST concentrations in serum together with decreased mRNA and protein expressions of Nrf2 pathway related molecules (Nrf2, HO-1, NQO1); and increased mRNA and protein expressions of Keap1. However, the supplement of copper sulfate (CuSO4) significantly ameliorated the changes mentioned above. Our results indicate that Cu deficiency can cause hepatic damage in mice is associated with the activation of oxidative stress and inhibition of Nrf2 pathway.

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Data Availability

Data available on request due to restrictions privacy. The data presented in this study are available on request from the corresponding author. The data are not publicly available due to this paper is part of a series of studies, and disclosure of data may influence the publication of subsequent papers.

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Funding

This work was supported by Sichuan Mianyang 404 Hospital (No: 404–220611).

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Authors and Affiliations

  1. Sichuan Mianyang 404 Hospital, Mianyang, 621010, Sichuan, People’s Republic of China

    Zhiying Pan, Chengfeng Deng, Lian Shui & Bing Liu

  2. School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, 621010, Sichuan, People’s Republic of China

    Heng Yin

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  1. Zhiying Pan
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Zhiying Pan, Bing Liu, and Heng Yin designed and performed experiments, collected and analyzed data, and wrote the paper. Chengfeng Deng and Lian Shui performed experiments. All authors contributed discussions and interpretations.

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Correspondence to Bing Liu.

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Pan, Z., Deng, C., Shui, L. et al. Copper Deficiency Induces Oxidative Stress in Liver of Mice by Blocking the Nrf2 Pathway. Biol Trace Elem Res 202, 1603–1611 (2024). https://doi.org/10.1007/s12011-023-03769-y

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